Our previous studies have illustrated that CacyBP/SIP (Calcyclin-binding protein or Siah-1-interacting protein) promoted the proliferation of glioma cells. However, the possible mechanism still needs to be clarified. In the current study, we aimed to uncover the potential mechanism of CacyBP/SIP in regulating glioma cell proliferation. We found that CacyBP/SIP decreased the protein level of p53, but not the mRNA level of p53 in p53 mutant U251 cell line, whereas, in p53 wild-type U87 cell line, CacyBP/SIP neither promoted its proliferation nor regulated the changes of p53 protein. Further investigation indicated that CacyBP/SIP interacted with p53 and Mdm2 (Mouse double minute 2) to promote p53 ubiquitination and subsequent proteasome-mediated degradation in U251. Moreover, in the presence of Mdm2, CacyBP/SIP boosted the ubiquitination of p53 in a dose-dependent manner. On the contrary, inhibition of Mdm2 activity significantly increased the stability of p53. Finally, we found that the protein level of CacyBP/SIP and p53 is inversely correlated in p53 mutant human glioma tissues. These observations suggest an underlying mechanism that CacyBP/SIP promotes the degradation of p53 by enhancing Mdm2 E3 ligase activity, which reveals a novel pathway for the regulation of mutant p53 and provides a new therapeutic approach to target the CacyBP/SIP-induced glioma cell proliferation.Pancreatic ductal adenocarcinoma (PDAC) is now the 11th most common cancer and in 2018 there were 458,918 new cases worldwide. In the Czech Republic, a total of 2,173 patients were diagnosed in 2015, ranking the second in incidence worldwide. In contrast to other malignancies, recent research has not brought any major breakthrough in the treatment of PDAC and hence the prognosis remains very serious. Radical resection is the only curative approach, but after the initiation of the standard pathological evaluation of the resected tissue, according to the Leeds protocol, 80% of the resections are R1 (resections with microscopically positive margins). The results of studies in patients with borderline resectable or locally advanced PDAC prefer neoadjuvant chemotherapy or chemoradiotherapy. This approach leads to a higher number of radical R0 resections and better survival. For neoadjuvant treatment in patients with primarily resectable PDAC, most results come from retrospective analysis or phase II trials. However, recently, data from three randomized clinical trials with neoadjuvant therapy for resectable PDAC were presented. These results support the use of chemotherapy or chemoradiotherapy prior to surgery. In the trials published to date, there are differences in chemotherapeutic regimens, cytostatic doses, and the definition of resectability. Thus, up-front resection with adjuvant chemotherapy is still the standard of care and a well-designed randomized trial using neoadjuvant therapy is now necessary.Glioma is the most common type of brain cancer. https://www.selleckchem.com/products/tp-0903.html Chemotherapy combination with surgery and radiotherapy is a standard treatment for patients. Although there are many advances in glioma therapy, the prognosis of glioma patients has not significantly been improved over the past decades. Hence, there is still an urgent need to develop a new therapy to treat glioma. Cell viability was assessed by CellTiter Blue assay; flow cytometry (FCM) was used for detecting cell apoptosis; ROS detection was detected by ROS Assay; H2O2 detection was performed by hydrogen peroxide detection kits; real-time PCR and WB were used to determine gene expression. Using the glioma cell line U251 and U87, we investigated a possible combination inhibitory effect includes metformin and cold atmospheric plasma (CAP). The combination treatment showed a synergistic inhibitory effect on cell viability, significantly inducing cell apoptosis. Furthermore, we also found H2O2 produced by CAP has an important role in the synergistic inhibitory effect, eliminating H2O2 with catalase reversed the synergistic inhibitory effect. In addition, the transcript and protein levels of c-FOS were robustly increased after co-treated with metformin and CAP. Taken together, we propose that pre-treatment of glioma cells with metformin sensitize tumor cells to CAP, which may serve as a potential therapeutic strategy for glioma.The aim of this study was to evaluate the diagnostic performance and the utility of F-18-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) in the clinical management of patients presenting with lymph node metastasis of undefined primary origin (CUP). A total of 53 patients (34 males, 19 females) with a diagnosis of lymph node metastasis according to the histopathology and/or conventional imaging were enrolled in this retrospective study. Patients were divided into four groups according to the initial location of their metastasis - group 1, cervical lymph nodes (n=39), group 2, axillary lymph nodes (n=6), group 3, mediastinal lymph nodes (n=2) and group 4, abdominal and pelvic lymph nodes (n=6). The site of a probable primary malignancy suggested by PET/CT was confirmed by biopsy/further investigations or follow-up. 18F-FDG PET/CT accurately detected the primary carcinoma in 19 of 53 patients (36%), with head and neck cancer and lung carcinoma being the most common primary locations. The PET-CT scan results were negative for primary site localization in 13% of patients (false-negative), while 45% had true negative results, and 6% displayed false-positive results. Additional distant metastatic foci were identified in 21 of all patients (40%). The overall sensitivity, specificity, and accuracy rates of the study were identified as 73%, 89%, and 81%, respectively; in the group with cervical lymph node metastasis sensitivity 70% and specificity 84%. To conclude, 18F-FDG PET/CT is a sensitive and selective procedure for detecting unknown primary tumors, especially in the clinical setting of cervical lymph node metastasis and its use should be encouraged earlier in the pre-treatment phase of CUP-patients, leading to higher detection of probable primary sites, guiding subsequent biopsy, and more accurate detection of distant metastases in a single examination.